tbuckley/cabot-search huggingface dataset:
IMMU-09. Interim analysis from BrainChild-03: Seattle Children’s Locoregional B7-H3 CAR T Cell Trial for Children with Recurrent Central Nervous System Tumors and DIPG
Authors: Nicholas Vitanza, Juliane Gust, Ashley Wilson, Wenjun Huang, Dickson Chen, Michael Meechan, Matt Biery, Carrie Myers, Sophie Tahiri, Erin Crotty, Sarah Leary, Bonnie Cole, Samuel Browd, Jason Hauptman, Amy Lee, Catherine Albert, Navin Pinto, Rimas Orentas, Rebecca Gardner, Michael Jensen, Julie Park
Journal: Neuro-Oncology (2022)

Abstract BrainChild-03 is a phase 1 clinical trial delivering repeated locoregional 2nd generation B7-H3 CAR T cells with 4-1BB co-stimulation to children with central nervous system (CNS) tumors without lymphodepleting chemotherapy. The primary endpoints are feasibility and safety, with secondary endpoints of disease response and correlatives of CAR T cell activity. There are 3 arms: (A) – weekly delivery into the tumor cavity, (B) – weekly delivery into the lateral ventricle for metastatic disease, (C) – biweekly delivery into the lateral ventricle for diffuse intrinsic pontine glioma (DIPG). In total, 23/24 (96%) enrolled patients have had successful CAR T manufacturing. 16/24 patients are evaluable and have received a total of 141 intracranial CAR T cell doses. Unevaluable patients include 5 never treated and 3 who progressed prior to receiving the minimum doses to become evaluable. The most common adverse events have been headache (16/16, 100%), nausea/vomiting (12/16, 75%), and fever (10/16, 63%). There has been 1 DLT for an intratumoral hemorrhage and no cytokine release syndrome (CRS). 7 evaluable patients with DIPG (Arm C) have received a cumulative 50 infusions. 5/7 DIPG patients enrolled after progression and have a median survival of 246.5 days post-initial CAR T cell infusion, with 4/5 still alive. The 2 DIPG patients enrolled prior to progression had radiographic improvement, including 1 with improvement of a cranial nerve 6 palsy who self-withdrew from protocol therapy after 18 infusions over 12 months and 1 still on protocol therapy after 11 infusions over 6 months. DIPG patients have had increased CSF levels of proinflammatory mediators (e.g. CXCL10, CCL2, IFNg, GM-CSF, IL-12) without systemic cytokine changes. 5/7 DIPG patients had detectable CAR T cells in their CSF post-infusion. Ultimately, the preliminary experience suggests locoregional delivery of B7-H3 CAR T cells may be feasible and tolerable in children with CNS tumors, including DIPG.
Impact of obesity in the management of kidney cancer, study URO-CCR n°87
Authors: L. Surlemont, J-C. Bernhard, C-K. Bensalah, F. Audenet, P. Bigot, N. Doumerc, A. De La Taille, M. Roupret, J. Olivier, F. Bruyère, B. Parier, H. Lang, M. Brenier, T. Waeckel, J-A. Long, M. Durand, N. Branger, R. Tambwe, O. Cussenot, R. Boissier, T. Charles, F-X. Nouhaud
Journal: European Urology (2022)
Deciphering the role of Store Operated Ca2+ entry in post-ischemic angiogenesis
Authors: I Galeano-Otero, R Del Toro, I Mayoral-Gonzalez, A Ordonez-Fernandez, T Smani
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Agencia Estatal de Investigación Background Post-ischemic angiogenesis is essential to improve tissue repair and heart recovery after myocardial infarction (MI). This process is tightly controlled by pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), which in turn promotes signaling pathways involving the increase in the intracellular Ca2+ concentration ([Ca2+]i). Recently, we demonstrated that store-operated calcium entry (SOCE) plays a key role in angiogenesis. However, the function of SOCE in post-ischemic angiogenesis remains unknown. The aim of this study is to explore the role of SOCE in this crucial repairing process. Materials and methods In vitro angiogenesis was studied using Human Umbilical Vein Endothelial Cells (HUVEC) for tube formation assay over Matrigel supplemented with serum from rat model of ischemia/reperfusion (I/R) and from ST elevation MI (STEMI) patients who underwent primary percutaneous coronary intervention (pPCI). We evaluated serum VEGF-A levels using ELISA. Genes and protein expression was determined by RT-qPCR and western blot, respectively. HUVEC migration was assessed by wound healing assay. Moreover, changes in [Ca2+]i were measured using fura-2 AM. Results We found that STEMI patients had higher levels of circulating VEGF-A, as compared to controls. The incubation of HUVEC seeded on Matrigel with the serum of these patients promoted vessels-like formation since it enhanced the number of meshes and junctions. Likewise, serum from I/R rats also boosted HUVEC angiogenesis over Matrigel and promoted faster gap closure in wound healing assay, as compared to cells incubated with sham rats’ serum. Furthermore, serum from both rats and patients modulated the expression Hes1 and Hey1, well-known mediators of Notch1 signaling pathway. Moreover, we found that knockdown of Orai1, the pore-forming subunit of the store-operated calcium channel (SOCC), using siRNA impairs VEGF-mediated [Ca2+]i increase, as well as HUVEC tube formation, proliferation, and migration. Conclusion Our data show for the first that serum from both STEMI patients and I/R rats promote angiogenesis, involving Orai1 and Notch1 signaling pathways.
Robot-assisted video-endoscopic radical inguinal lymphadenectomy for penile cancer: surgical anatomy and technique
Authors: A. Brassetti, A. Bove, U. Anceschi, M.C. Ferriero, S. Guaglianone, R. Mastroianni, L. Misuraca, G. Tuderti, G. Simone
Journal: European Urology (2022)
EPEN-04. Refinement of molecular and clinical characteristics in a cohort of 1,801 ependymomas
Authors: Lara Pohl, Denise Obrecht, Leonille Schweizer, Annika Wefers, Stefan Rutkowski, Michael Bockmayr, Ulrich Schüller
Journal: Neuro-Oncology (2022)

Abstract DNA methylation profiling led to the definition of ten molecular types of ependymomas with distinct biological and clinical features. The largest published reference cohort consists of 500 ependymomas encompassing nine molecular types that were known at this point. Our study aimed to confirm and refine molecular and clinical characteristics of ependymoma types and subtypes based on a considerably larger, well-annotated cohort of ependymal tumors. Here, we analyzed previously published and newly generated DNA methylation profiles, generated on the Illumina 450k and EPIC arrays, from a total of n=1,801 ependymomas. We looked at both global DNA methylation as well as inferred copy number profiles and correlated these data with clinical parameters. Patients with EPN-PFA, EPN-RELA, and EPN-MYCN tumors showed the worst outcome with 10 year-overall survival rates of 56%, 64%, and a 5 year-overall survival rate of 73%, respectively. EPN-PFA, the most frequent tumor type in our series, occurred in children in &amp;gt;98% of cases, epigenetically split into two major subtypes, and harbored chromosome 1q gains and 6q losses as markers for worse survival (p&amp;lt;0.0001 and p=0.042, respectively). In supratentorial EPN-RELA, a combined loss of CDKN2A/B indicated a worse survival compared to the wildtype (p=0.0004), but the loss of only CDKN2A or CDKN2B did not. Ten out of 169 EPN-RELA were located in the posterior fossa, and Kaplan Meier estimators showed that these tumors relapsed or progressed even earlier than supratentorial cases with a combined loss of CDKN2A/B (p=0.0062). SP-MPE and PF-SE, which are generally regarded as non-aggressive tumors, only had a 10-year progression-free survival of 60% and 63%, respectively, in our series. In ongoing analyses, we are training machine learning algorithms to more accurately predict survival and response to treatments. These methods shall help clinicians make informed decisions regarding treatment options on new patients.
EPID-02. Survival Experience in Pediatric Patients of Central Nervous System (CNS) Tumour in Canada
Authors: Yan Yuan, JiaQi Liu, Emily Walker, Faith Davis
Journal: Neuro-Oncology (2022)

Abstract Established in 2016, the Brain Tumour Registry of Canada Surveillance Research Collaboration aims to address the lack of detailed information on CNS tumours in Canada. Using Canadian Cancer Registry (CCR) data with linked vital status, we present survival estimates for all primary CNS tumours (excluding Quebec) among pediatric patients (age 0-14). Pediatric patients diagnosed with primary CNS tumours during 2010-2017 were included. Vital status was obtained by Statistics Canada through linkage to the Canadian Vital Statistics Database and the income tax returns file, with a cut-off date of December 31, 2017. We used the Pohar-Perme method to estimate the net survival rate (NSR) through the period approach. International Classification of Diseases for Oncology (3rd edition) site/histology codes were grouped into 25 histological categories, irrespective of tumour behaviour, according to the schema developed by the Central Brain Tumor Registry of the United States. Of 1725 pediatric CNS tumours, the 1-, 2- and 5-year NSR are 0.89 (95%CI 0.87-0.90), 0.84 (95%CI 0.81-0.86) and 0.80 (95%CI 0.78-0.82), respectively. All non-malignant CNS tumours have a median survival over 8 years. The 5-year NSR range from 0.90 (95%CI 0.47-0.99) for unique astrocytoma variants, 0.95 for tumour of sellar region (95%CI 0.85-0.98) and germ cell tumours, cysts and heterotopias (95%CI 0.67-0.99), to 1.0 for choroid plexus tumours, tumours of cranial and spinal nerves, and meningioma. For malignant CNS tumours, NSR vary greatly depending on histology grouping. 5-year NSR from lowest to highest are glioblastoma (0.10, 95%CI 0.03-0.23), anaplastic astrocytoma (0.19, 95%CI 0.05-0.40), glioma not otherwise specified (0.54, 95%CI 0.46-0.62), embryonal tumours (0.72, 95%CI 0.65-0.79), diffuse astrocytoma (0.74, 95%CI 0.59-0.85), ependymal tumours (0.78, 95%CI 0.67-0.87), germ cell tumours, cysts and heterotopias (0.85, 95%CI 0.70-0.93) and pilocytic astrocytoma (1.0). We report the most comprehensive and up-to-date data on the pediatric primary CNS tumour survival experience in Canada.
The efficacy and safety of taletrectinib in patients with TKI-naïve or crizotinib-pretreated ROS1-positive non–small cell lung cancer (NSCLC).
Authors: Wei Li, Nong Yang, HuiWen Ma, Huijie Fan, Kunyan Li, Huijuan Wu, Qitao Yu, Yongsheng Wang, Xue Meng, Xicheng Wang, Xintian Qin, Ziping Wang, Yunpeng Liu, Min Tao, Wu Zhuang, Yong Fang, Ping Sun, Kaihua Lu, Jingxun Wu, Caicun Zhou
Journal: Journal of Clinical Oncology (2022)

8572 Background: Taletrectinib (AB-106 / DS-6051b) is a next-generation, potent, CNS- penetrant, selective ROS1 tyrosine kinase inhibitor. The ongoing TRUST study (NCT04395677) is a multicenter, open-label, single-arm, Phase 2 study of taletrectinib in Chinese ROS1-positive NSCLC patients who are TKI -naïve or crizotinib-pretreated. Here we present the updated efficacy and safety results of the study. Methods: The eligible ROS1-positive NSCLC patients were enrolled into either TKI-naïve or crizotinib-pretreated cohorts, and treated with taletrectinib 600mg once daily. The study endpoints included overall response rate (ORR), duration of response (DOR), disease control rate (DCR), overall intracranial response rate (IC-ORR), progression-free survival (PFS), and safety profile. Results: As of the data cutoff date of September 7, 2021, 61 of the 86 stage IV patients enrolled in the study have at least three postbaseline tumor assessment of which 40 patients in the TKI-naïve cohort, and 21 patients in the crizotinib-pretreated cohort (50% patients having at least one prior chemotherapy). In the TKI -naïve cohort, the confirmed ORR by investigators per RECIST 1.1 was 90.0%: [95%CI: 76.3%; 97.2%] (36/40); and the DCR was 95% [95%CI: 83.1%; 99.4%] (38/40). In the crizotinib-pretreated cohort, the confirmed ORR by investigators was 47.6% [95%CI: 25.7%; 70.2%] (10/21); and DCR was 76.2%: [52.8%; 91.8%] (16/21). The mDOR and mPFS are not reached yet for both cohorts. Of 6 patients having brain metastasis and measurable target brain lesions at baseline, the intracranial ORR and IC-DCR were 83.3% and 100%, respectively. Of 4 patients with ROS1 G2032R mutation, 3 patients achieved partial response (PR), and 1 patient achieved stable disease (SD). The most common treatment-related adverse events (TRAEs) include diarrhea, nausea, vomiting, transaminase elevation, anemia, neutrophil count decrease, etc. were Grade 1 or 2, and the most common AEs (below 10%) were ALT/AST increased but reversible. Conclusions: Taletrectinib demonstrated meaningful clinical efficacy in both TKI-naïve and crizotinib-pretreated ROS1 positive NSCLC patients. In particular, taletrectinib showed clinical effectiveness in patients with ROS1 secondary G2032 mutations and patients with brain metastasis. Taletrectinib was well tolerated in this patient population. Clinical trial information: NCT04395677.
DIPG-13. Immune profiling by RNA-seq deconvolution and single-cell sequencing reveal myeloid cell enrichment in DIPG tumor microenvironment
Authors: Xiaoting Zhu, Deepak Mishra, Shiva Senthil Kumar, Todd Mchugh, Margot Lazow, Maryam Fouladi, Rachid Drissi
Journal: Neuro-Oncology (2022)

Abstract Diffuse intrinsic pontine glioma (DIPG) remains an incurable disease with median overall survival &amp;lt;12 months despite decades of clinical trials investigating multimodal therapies. Immunotherapy represents a promising treatment paradigm which has been successfully used in other cancers. An adequate understanding of the tumor microenvironment and immunologic profile is essential to identify potential immunotherapeutic targets to inform immunotherapy design. Previous studies have shown that most DIPG tumors harbor low mutational burden compared to adult cancers and are characterized by a non-inflammatory microenvironment, limiting the development of immunotherapies in this disease. Our team’s prior work similarly demonstrated that most DIPG tumors have an immunologically “cold” microenvironment, but a subset of tumors harbors a more inflammatory gene expression profile and/or higher mutational burden, with trends toward improved survival and favorable radiographic response to radiation. Here, we applied a deconvolution analysis using CIBERSORTx on bulk RNA-seq data from 28 DIPG patients’ tumors paired with matched normal tissue specimens, to profile the immune microenvironment of DIPG and evaluate immune-related gene expression to determine percentages of different types of immune cells. Our results indicate that DIPGs have very limited lymphocyte infiltration. However, the infiltration of macrophages “M2-like” type cells and CD4 memory resting T cells were significantly higher in tumors compared to normal tissue samples. Similar results were found using single-cell RNA sequencing performed on biopsy and autopsy tissue, with less than 5% of total cells identified as immune cells. MHC I components were widely expressed in DIPGs with no significant difference between tumor and normal tissue. Expression of CD11B and CD68 were higher in tumor compared to normal tissue, suggesting enrichment of myeloid cells. Overall, deconvolution analysis of bulk RNA-seq can be used to profile DIPG tumors’ immune microenvironment to aid in the thoughtful design of effective immunotherapeutic strategies for this disease.
Patterns of care and survival outcomes for young women treated for early breast cancers in a community hospital system.
Authors: Aye Thet, Tarik H. Hadid, Judith Boura, Narendra Gohel, Jeffrey Falk, Maria T. Vlachaki, Allison Jay, Paul J. Chuba
Journal: Journal of Clinical Oncology (2022)

e12586 Background: Younger women with breast cancer have relatively poor prognosis and higher rates of locoregional recurrence. Epidemiologic data suggest equivalent survival with mastectomy or breast conserving surgery (BCS) in this population. We analyzed patterns of care and survival outcomes for women aged &lt; 45 years with breast cancer treated at Ascension Macomb Oakland Hospital (AMOH), Ascension St John Hospital (ASJH), and Ascension Providence Hospital (APH). Methods: Between 2006 and 2015 there were 4703 patients treated for breast cancers at AMOH, ASJH, and APH. We identified a subset of 319 patients aged &lt; 45 treated for breast cancers and investigated patients' tumor characteristics, type of surgery, and overall survival by using the Metric database and reviewing patient charts. Kaplan-Meier analysis and log-rank tests together with univariate analysis was done by using SAS for Windows 9.4. Results: With median follow-up of 53 months among living patients, 26 patients had died. African American race was associated with decreased overall survival (log-rank p=0.0031). Factors associated with improved overall survival included AJCC stage grouping (p=0.009), estrogen receptor (p=0.0004) or progesterone receptor positivity (p=0.005), or HER2 negativity (p=0.039). Similarly, survival was different according to grouping cases as luminal A (n=174), luminal B (n=39), basal (n=46), HER2 (n=23) and unknown phenotype (n=37) (P=0.008). Considering all cases 91 were treated with BCS (28.5%) and 228 with mastectomy (71.4%; 113 unilateral and 115 bilateral with or without reconstruction). Conclusions: In this group of young women, overall survival was influenced by stage and breast cancer phenotype as expected. African American race was associated with inferior overall survival. We found high rates of mastectomy with or without reconstruction. In the future comprehensive disease profiling will help to direct decision making.
Outcomes of single-agent PD-(L)-1 versus combination with chemotherapy in patients with PD-L1-high (≥ 50%) lung cancer.
Authors: Arielle Elkrief, Joao Victor Machado Alessi, Biagio Ricciuti, Hira Rizvi, Isabel Ruth Preeshagul, Jacklynn V. Egger, Jamie E. Chaft, Charles M. Rudin, Gregory J. Riely, Mark G. Kris, Marc Ladanyi, Matthew D. Hellmann, Mark M. Awad, Adam Jacob Schoenfeld
Journal: Journal of Clinical Oncology (2022)

9052 Background: Single agent PD-(L)-1 blockade (IO) and PD-(L)-1 blockade combined with chemotherapy (ChemoIO) are both standard first-line treatments for patients with PD-L1-high (≥ 50%) metastatic non-small cell lung cancer (NSCLC). These regimens have not been compared prospectively, so comparative effectiveness is unclear. It is also unknown if clinical and molecular tumor characteristics differentially associate with benefit to IO vs ChemoIO in patients with NSCLC with high PD-L1 tumor expression. Methods: All patients with metastatic NSCLC treated with IO or ChemoIO at two institutions (Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute) were reviewed. Patients with EGFR or ALK alterations, PD-L1 expression &lt; 50%, treated with IO or ChemoIO in &gt; 1 st line setting were excluded. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were compared between the IO vs ChemoIO groups and association with clinical, pathologic, and molecular features was examined. To account for NGS panel differences, tumor mutational burden (TMB) values were harmonized using a z-score conversion as previously described (Vokes et al, 2019). Results: Of 639 patients with stage IV EGFR/ ALK wild-type NSCLC and PD-L1 ≥50% treated in the 1 st line setting, 504 received IO and 135 received ChemoIO. Baseline ECOG performance status (p = 0.3), median PD-L1 % (p &gt; 0.9) and TMB (p = 0.2) were similar between the IO and ChemoIO groups. For patients receiving IO vs ChemoIO, there was no significant difference in OS (HR 0.8, 95% CI 0.6 to 1.08; p = 0.2). Median PFS was shorter (HR 0.7, 95% CI 0.6 to 0.9; p = 0.004) and ORR was lower (40% IO vs 55% ChemoIO, p = 0.002) in the IO group. Among patients with durable responses (&gt; 6 months), never smokers were less common in the IO group (6% vs 18%, p &lt; 0.001), but there was no difference in PD-L1 expression, TMB, or mutational ( KRAS, STK11, or KEAP1) profile to suggest differential predictors of benefit to IO or ChemoIO. Conclusions: In patients with PD-L1 high NSCLC, there was no survival benefit associated with the addition of chemotherapy to IO. There were also no clear differences in PD-L1 expression or molecular features associated with durable response to IO vs ChemoIO. These findings have implications for treatment selection in this population.
Early metabolic syndrome in testicular germ cell tumors : A prospective study from India.
Authors: Prashant Pandey, Deepak Dabkara, Sandip Ganguly, Joydeep Ghosh, Somnath Roy, Debapriya Mondal, Sujoy Gupta, Reena Nair, Bivas Biswas
Journal: Journal of Clinical Oncology (2022)

e17010 Background: Metabolic syndrome (MS) is a known complication in patients of testicular germ cell tumors . Early metabolic syndrome is not well-defined and literature on the same is scarce. Methods: This is a single institutional prospective cohort study of patients with testicular germ cell tumors from Jan’2020 to June 2021 with a minimum follow-up of 6 months after treatment completion. Patients were evaluated for MS as per NCEP ATP (National Cholesterol Education Program Adult Treatment Plan) III criteria and partial MS was defined if any one abnormal criteria was present. Clinicopathologic and treatment characteristics were correlated with development of MS. Results: Thirty-six (25 nonseminomatous tumor and 11 seminoma) were included with median age of 29 yrs (range: 18-44). Treatment protocol was - platinum based chemotherapy [BEP (n = 7), EP(n = 18),VIP(n = 4) ]in 81% (n = 29/36), single agent carboplatin in 8% (n = 3/36), and surveillance only in 11% (n = 4/36) patients. Incidence of complete metabolic syndrome noted in 42% (n = 15) and partial metabolic syndrome in 36% (n = 13) of patients after median follow-up of 13.2 months (range-6-22). Deranged parameters detected were - high serum triglyceride (≥150 mg/dl) in 64% (n = 23/36), low serum HDL cholesterol (&lt; 40 mg/dl) in 53% (n = 19/36), high blood pressure (≥130/85 mm of Hg) in 47% (n = 17/36), high waist circumference (&gt; 110 cm) in 6% (n = 2/36) and high fasting plasma glucose (≥5.6 mmol/L) in 22% (n = 8/36) of patients. Median weight gain was 5 Kg (range: 2-14). The median time to development of metabolic syndrome was 143 days (range: 90-461). Hypogonadism (testosterone &lt; 433ng/dl.) showed positive correlation (degree of freedom = 0.3143) and C-reactive protein showed negative correlation (degree of freedom -0.3090) with MS, respectively. Conclusions: Majority of Testicular germ cell tumor patients (n = 28, 78%) had features of early MS, irrespective of treatment modalities. Patients with hypogonadism are more likely to develop early MS. Larger prospective studies are warranted to assess the incidence of early MS in patients with testicular germ cell tumors and to formulate appropriate health intervention to mitigate its significant long-term effects on mortality and morbidity.